STRESS-INDUCED MODULATION OF THE TUMOR MICROENVIRONMENT: MECHANISMS AND IMPLICATIONS FOR CANCER PROGRESSION.

Abstract

Chronic stress is one of the key exogenous factors that can significantly affect tumor cell biology by disrupting the regulation of the tumor microenvironment (TME), thereby promoting the manifestation of the malignant process. Activation of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system induced by stressors leads to the secretion of glucocorticoids and catecholamines, which contribute to the deregulation of microenvironmental components that determine the aggressiveness of malignant neoplasms. This review systematizes the current views on the impact of stress-induced signals on the immune, stromal, vascular, and metabolic components of the TME and analyzes their contribution to the formation of an aggressive tumor phenotype. Particular attention is given to the interplay between neurohumoral stress, the gut, and the intratumoral microbiome, forming a complex networked environment supporting tumor progression. Advancing the understanding of molecular interactions between stress mediators and cellular elements of the TME will provide a foundation for developing innovative therapeutic strategies targeting not only the tumor itself but also minimizing the adverse effects of stress on individual components of the TME.